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Aggregation of human mesenchymal stem cells enhances survival and efficacy in stroke treatment
In this study, we report the effects of short-term preconditioning of hMSCs via three-dimensional (3D) aggregation on stroke lesion recovery after intra-arterial (IA) transplantation of 3D aggregate-derived hMSCs (Agg-D hMSCs) in a transient middle cerebral artery occlusion (MCAO) stroke model. Compared with two-dimensional (2D) monolayer culture, Agg-D hMSCs exhibited increased resistance to ischemic stress, secretory function and therapeutic outcome. Short-term preconditioning via 3D aggregation reconfigured hMSC energy metabolism and altered redox cycle, which activated the PI3K/AKT pathway and enhanced resistance to in...
Source: Cytotherapy - September 17, 2019 Category: Cytology Source Type: research

Multinuclear MRI Reveals Early Efficacy of Stem Cell Therapy in Stroke
Transl Stroke Res. 2022 Jul 28. doi: 10.1007/s12975-022-01057-w. Online ahead of print.ABSTRACTCompromised adult human mesenchymal stem cells (hMSC) can impair cell therapy efficacy and further reverse ischemic recovery. However, in vitro assays require extended passage to characterize cells, limiting rapid assessment for therapeutic potency. Multinuclear magnetic resonance imaging and spectroscopy (MRI/S) provides near real-time feedback on disease progression and tissue recovery. Applied to ischemic stroke, 23Na MRI evaluates treatment efficacy within 24 h after middle cerebral artery occlusion, showing recovery of sodiu...
Source: Cell Research - July 28, 2022 Category: Cytology Authors: Shannon Helsper Xuegang Yuan F Andrew Bagdasarian Jacob Athey Yan Li Cesario V Borlongan Samuel C Grant Source Type: research

Defective Function of the Blood-Brain Barrier in a Stroke-Prone Spontaneously Hypertensive Rat: Evaluation in an In Vitro Cell Culture Model.
Abstract The blood-brain barrier (BBB) comprises three cell types: brain capillary endothelial cells (BECs), astrocytes, and pericytes. Abnormal interaction among these cells may induce BBB dysfunction and lead to cerebrovascular diseases. The stroke-prone spontaneously hypertensive rat (SHRSP) harbors a defective BBB, so we designed the present study to examine the role of these three cell types in a functional disorder of the BBB in SHRSP in order to elucidate the role of these cells in the BBB more generally. To this end, we employed a unique in vitro model of BBB, in which various combinations of the cells cou...
Source: Cellular and Molecular Neurobiology - July 8, 2020 Category: Cytology Authors: Nakagawa S, Ohara H, Niwa M, Yamagata K, Nabika T Tags: Cell Mol Neurobiol Source Type: research

Enhanced Neurogenesis and Collaterogenesis by Sodium Danshensu Treatment After Focal Cerebral Ischemia in Mice.
Abstract Ischemic stroke remains a serious threat to human life. There are limited effective therapies for the treatment of stroke. We have previously demonstrated that angiogenesis and neurogenesis in the brain play an important role in functional recovery following ischemic stroke. Recent studies indicate that increased arteriogenesis and collateral circulation are determining factors for restoring reperfusion and outcomes of stroke patients. Danshensu, the Salvia miltiorrhiza root extract, is used in treatments of various human ischemic events in traditional Chinese medicine. Its therapeutic mechanism, however,...
Source: Cell Transplantation - April 1, 2018 Category: Cytology Authors: Wei ZZ, Chen D, Liu LP, Gu X, Zhong W, Zhang YB, Wang Y, Yu SP, Wei L Tags: Cell Transplant Source Type: research

Extended Ischemic Recovery After Implantation of Human Mesenchymal Stem Cell Aggregates Indicated by Sodium MRI at 21.1 T
Transl Stroke Res. 2022 Feb 7. doi: 10.1007/s12975-021-00976-4. Online ahead of print.ABSTRACTExtended therapeutic application remains a significant issue in the use of stem cell therapies to treat ischemic stroke. Along these lines, neurological recovery in a rodent model of ischemic stroke was evaluated following implantation of human mesenchymal stem cell aggregates (hMSC-agg), labeled with micron-sized particles of iron oxide, directly into the lateral ventricle contralateral to the ischemic lesion hemisphere. Longitudinally, disease progression and response to hMSC-agg therapy were assessed by 1H and 23Na magnetic res...
Source: Cell Research - February 8, 2022 Category: Cytology Authors: Shannon Helsper F Andrew Bagdasarian Xuegang Yuan Kaya Xu Jea-Young Lee Jens T Rosenberg Cesario V Borlongan Teng Ma Samuel C Grant Source Type: research

Transcriptional and epigenetic regulation of ncx1 and ncx3 in the brain.
Abstract Sodium-calcium exchanger (NCX) 1 and 3, have been demonstrated to play a relevant role in controlling the intracellular homeostasis of sodium and calcium ions in physiological and patho-physiological conditions. While NCX1 and NCX3 knocking-down have been both implicated in brain ischemia, several aspects of the epigenetic regulation of these two antiporters transcription were not yet well characterized. In response to stroke, NCX1 and NCX3 transcriptional regulation occurs from specific promoter sequences. Several evidences have shown that the expression of NCX1 and NCX3 can be determined by epigenetic m...
Source: Cell Calcium - March 6, 2020 Category: Cytology Authors: Formisano L, Guida N, Mascolo L, Serani A, Laudati G, Pizzorusso V, Annunziato L Tags: Cell Calcium Source Type: research

HDAC9 in the Injury of Vascular Endothelial Cell Mediated by P38 MAPK Pathway
In this study, we explored the effect of HDAC9 on the P38 mitogen activated protein kinase (P38 MAPK), a classic cellular inflammation-related pathway, by knocking down HDAC9 in vascular endothelial cells with short hairpin RNA (shRNA) and found that HDAC9 may mediate oxidized low density lipoprotein (ox-LDL)-induced inflammatory injury in vascular endothelial cells by regulating the phosphorylation level of P38 MAPK to lead to AS. It can be seen that HDAC9 may be a target to control the formation of atherosclerotic plaques. In follow-up experiments, it was verified that sodium valproate (SVA), as a HDAC9 inhibitor, can in...
Source: Cell Research - December 22, 2021 Category: Cytology Authors: Xi Kuang Shuang Chen Jitong Lao Yongmin Chen Dandan Jia Linzhi Tu Lin Ma Xiaoping Liao Wenjie Zhao Qifu Li Source Type: research

Increased atrial effectiveness of flecainide conferred by altered biophysical properties of sodium channels
Atrial fibrillation (AF) affects over 1% of the population and is a leading cause of stroke and heart failure in the elderly. A feared side effect of sodium channel blocker therapy, ventricular pro-arrhythmia, appears to be relatively rare in patients with AF. The biophysical reasons for this relative safety of sodium blockers are not known.Our data demonstrates intrinsic differences between atrial and ventricular cardiac voltage-gated sodium currents (INa), leading to reduced maximum upstroke velocity of action potential and slower conduction, in left atria compared to ventricle.
Source: Journal of Molecular and Cellular Cardiology - January 31, 2022 Category: Cytology Authors: Sian O' Brien, Andrew P. Holmes, Daniel M. Johnson, S. Nashitha Kabir, Christopher O' Shea, Molly O' Reilly, Adelisa Avezzu, Jasmeet S. Reyat, Amelia W. Hall, Clara Apicella, Patrick T. Ellinor, Steven Niederer, Nathan R. Tucker, Larissa Fabritz, Paulus K Source Type: research

Identification and characterization of the promoter and transcription factors regulating the expression of cerebral sodium/calcium exchanger 2 (NCX2) gene
Cell Calcium. 2022 Jan 23;102:102542. doi: 10.1016/j.ceca.2022.102542. Online ahead of print.ABSTRACTThe isoform 2 of sodium-calcium exchanger family (NCX2) is selectively expressed in neuronal and glial cells where it participates in Ca2+-clearance following neuronal depolarization, synaptic plasticity, hippocampal-dependent learning and memory consolidation processes. On the other hand, NCX2 is also involved in a neuroprotective effect following stroke. Despite the relevance of this antiporter under physiological and pathophysiological conditions, no studies have been reported on its genetic/epigenetic regulation. Theref...
Source: Cell Calcium - February 3, 2022 Category: Cytology Authors: Lucrezia Calabrese Angelo Serani Silvia Natale Valentina Tedeschi Natascia Guida Valeria Valsecchi Agnese Secondo Luigi Formisano Lucio Annunziato Pasquale Molinaro Source Type: research